This project is to research the use of anticancer antibodies labeled with radionuclides for cancer detection and localization by external scintigraphy. The attempt is to improve "cancer radioimmunodetection" by determining the best antibody forms and preparations, antibody labels, and imaging procedures and instrumentation. All three approaches are being pursued in model animal systems of human tumor xenografts and clinically. Known tumor markers, such as CEA, AFP, hCG, PAP, and CSAp, will serve as targets for radiolocalizing antibodies, since these have been found to enable the precise disclosure of a number of cancer types associated with these markers (gastro-intestinal, lung, liver, breast, testicular, ovarian, trophoblastic, and prostatic carcinomas). Diverse polyclonal (goat) and monoclonal (murine and human) antibodies will be further developed and evaluated experimentally and clinically. Other antigens associated with colorectal, mammary, and lung carcinomas will be identified by monoclonal antibody technology and evaluated in radioimmunodetection. Whole antibody IgG and fragments will be compared for improved imaging by planar and by emission tomographic methods. Both systemic and lymphoscintigraphic imaging will be undertaken. Improvements in background subtraction will be attempted by using one radionuclide on the antibody and a different isotope on the control (indifferent) IgG or myeloma protein. Another aspect of interest will be the use of combinations of antibodies, both against different epitopes of the same antigen and against different antigens of the same tumor type. The use of different metallic radionuclides conjugated to IgG, such as In-111 and Ru-97, also will be investigated. Although the major focus of this program is radioimmunodetection, the use of model systems to develop drug-conjugated antibodies for more selective therapy of colorectal carcinoma will be pursued. Finally, clinical immunotherapy with I-131-labeled antibodies will be undertaken in liver cancer patients (AFP antibodies) and in colorectal, pancreatic, and mammary carcinoma patients (CEA antibodies). The overall objective of this program is to institute an integrated program of cancer detection and therapy with anticancer antibodies which have been shown to accrete selectively in human cancers. (2)